RET finger protein enhances MBD2-and MBD4-dependent transcriptional repression
RET finger protein enhances MBD2-and MBD4-dependent transcriptional repression
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DOI：
10.1016/j.bbrc.2006.10.005
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发表时间：
2006-12-08
影响因子：
3.1
通讯作者：
Horii, Akira
中科院分区：
文献类型：
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作者：
Fukushige, Shinichi;Kondo, Emiko;Horii, Akira
我们最近证明MBD 4具有通过甲基-CpG抑制转录的能力，并且与CDKN 2A和MLH 1基因中的甲基化启动子相关。为了进一步研究MBD 4在基于甲基化的转录抑制中的作用，进行了酵母双杂交筛选，发现RET指蛋白（RFP）是与MBD 4中的转录抑制结构域相互作用的主要蛋白质之一。甲基化的CDKN 2A和MLH 1启动子中MBD 4介导的转录抑制的效果通过RFP的过表达而极大地增强。此外，RFP不仅与MBD 4而且与MBD 2或MBD 3形成蛋白质复合物，并且显示通过MBD 2增强转录抑制。这些结果表明，RFP是一个介体连接几个MBD蛋白，并允许形成一个更有效的转录抑制复合物。由于RFP已在多种肿瘤细胞系以及睾丸和胚胎中检测到高水平，RFP可能在肿瘤发生、精子发生和胚胎发生中通过MBD蛋白增强转录抑制中起重要作用。(c)2006年爱思唯尔公司All rights reserved.
We recently demonstrated that MBD4 possesses the ability to repress transcription through methyl-CpG and is associated with methylated promoters in the CDKN2A and MLH1 genes. In order to further investigate the role of MBD4 in methylation-based transcriptional repression, a yeast two-hybrid screening was performed, and the RET finger protein (RFP) was found to be one of the major proteins that interact with the transcriptional repression domain in MBD4. The effect of the MBD4-mediated transcriptional repression in methylated CDKN2A and MLH1 promoters was extremely enhanced by the overexpression of RFP. Furthermore, RFP forms a protein complex not only with MBD4 but also with MBD2 or MBD3 and was shown to enhance transcriptional repression through MBD2. These results suggest that RFP is a mediator connecting several MBD proteins and allowing the formation of a more potent transcriptional repressor complex. Because RFP has been detected at high levels in a variety of tumor cell lines as well as testis, and embryos, RFP may have an important role in the enhancement of transcriptional repression through MBD proteins in tumorigenesis, spermatogenesis, and embryogenesis. (c) 2006 Elsevier Inc. All rights reserved.